Magnetothermal nanoparticle technology alleviates parkinsonian-like symptoms in mice

• Published in: Nature communications Vol. 12; no. 1; pp. 5569 - 10
• Main Authors: Hescham, Sarah-Anna, Chiang, Po-Han, Gregurec, Danijela, Moon, Junsang, Christiansen, Michael G., Jahanshahi, Ali, Liu, Huajie, Rosenfeld, Dekel, Pralle, Arnd, Anikeeva, Polina, Temel, Yasin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-09-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - adverse effects; 6-Hydroxydopamine; 631/378/1689/1718; 631/378/2632/1323; 639/925; Animal models; Animals; Basal ganglia; Behavior, Animal - physiology; Brain; Capsaicin; Capsaicin receptors; Central nervous system diseases; Circuits; Connectors; Deep brain stimulation; Deep Brain Stimulation - methods; Disease Models, Animal; Electrical stimuli; Hardware; Hemorrhage; Hot Temperature; Humanities and Social Sciences; Implanted electrodes (biology); Invasiveness; Ion channels; Magnetic fields; Magnetite Nanoparticles - therapeutic use; Male; Mice; Mice, Inbred C57BL; Movement disorders; MPTP; multidisciplinary; Nanoparticles; Neural networks; Neural prostheses; Neurodegenerative diseases; Neurological diseases; Neuromodulation; Neurons - pathology; Oxidopamine - adverse effects; Pacemakers; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - therapy; Receptors; Science; Science (multidisciplinary); Signs and symptoms; Solitary tract nucleus; Stimulation; Subthalamic nucleus; Subthalamic Nucleus - physiology; Transient receptor potential proteins; TRPV Cation Channels - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25837-4

Deep brain stimulation (DBS) has long been used to alleviate symptoms in patients suffering from psychiatric and neurological disorders through stereotactically implanted electrodes that deliver current to subcortical structures via wired pacemakers. The application of DBS to modulate neural circuits is, however, hampered by its mechanical invasiveness and the use of chronically implanted leads, which poses a risk for hardware failure, hemorrhage, and infection. Here, we demonstrate that a wireless magnetothermal approach to DBS (mDBS) can provide similar therapeutic benefits in two mouse models of Parkinson’s disease, the bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and in the unilateral 6-hydroxydopamine (6-OHDA) model. We show magnetothermal neuromodulation in untethered moving mice through the activation of the heat-sensitive capsaicin receptor (transient receptor potential cation channel subfamily V member 1, TRPV1) by synthetic magnetic nanoparticles. When exposed to an alternating magnetic field, the nanoparticles dissipate heat, which triggers reversible firing of TRPV1-expressing neurons. We found that mDBS in the subthalamic nucleus (STN) enables remote modulation of motor behavior in healthy mice. Moreover, mDBS of the STN reversed the motor deficits in a mild and severe parkinsonian model. Consequently, this approach is able to activate deep-brain circuits without the need for permanently implanted hardware and connectors.
Deep-brain stimulation ameliorates parkinsonian symptoms, but it usually requires permanent implantation of hardware and connectors. Here, the authors show magnetothermal neuromodulation through the activation of TRPV1 can improve locomotor deficits in mouse models of Parkinson’s disease.